A Multisite Randomized Controlled Trial of Mindfulness Mediation Therapy for PTSD Background: Currently, veterans with posttraumatic stress disorder (PTSD) are typically treated with antidepressants which have limited efficacy and yield extremely low remission rates. New and improved treatments are sorely needed, especially in light of the inadequate evidence to support the efficacy of most pharmacologic and most psychotherapy treatments for PTSD. Complementary and Alternative Medicine practices, such as meditation, may fill this void. Several other illnesses often found in association with PTSD, such as chronic pain, anxiety, and depression, have shown positive response to meditation, specifically Mindfulness Based Stress Reduction (MBSR). MBSR is manualized program involving 8 weekly classes and a single 6-hour silent retreat session based on a systematic procedure to develop enhanced non-reactive awareness of the moment-to-moment experience of perceptible mental processes. MBSR is a well tolerated, already well disseminated. MBSR has been shown to be effective in reducing conditions that are commonly associated with PTSD, including pain, depression, anxiety and panic, and insomnia. Methods: We propose a prospective, randomized (1:1), controlled multisite study of MBSR in 180 veterans with PTSD. We will compare the clinical outcomes of MBSR to a credible group therapy control condition called Present Centered Group Therapy (PCGT). We will to evaluate the efficacy of MBSR in the treatment of PTSD, as defined by the Clinician Administered PTSD Scale (CAPS), a gold standard measure that is clinically relevant to PTSD. The CAPS will be rated by a trained assessor who is blind to the whether or not the participant receives the MBSR or PCGT intervention. Secondarily, we will evaluate the effects of MBSR on mindfulness, depression, PTSD symptom clusters, rates of response and evaluate the safety and tolerability of MBRS. We will also explore the subjects' acceptance of and satisfaction with MBSR, whether or not the subjects' treatment preference influences outcome; the stress-immunological-biomarkers as they relate to treatment outcome; and the durability of therapeutic effects of MBSR in the treatment of PTSD. Significance: Operations Enduring Freedom, Iraqi Freedom, and New Dawn have brought in large numbers of young men and women with war-related trauma and PTSD and have renewed our sense of mission. PTSD is a chronic and costly illness and treating PTSD is a VHA priority. Clinical trials of psychotherapeutic treatments for PTSD, particularly MBSR, are needed to fill the gap in knowledge and expand the evidence based treatment alternatives for veterans with PTSD.